Skived film for covering surface of plug for medical purposes, plug for medical purposes using said film, pre-filled syringe using said plug and method for producing said film

ABSTRACT

Provided is a PTFE skived film capable of exhibiting, with a single layer, sliding properties, barrier properties with regard to a liquid contact surface, and excellent tear resistance during injection molding. This skived film is characterized by being obtained by cutting a polytetrafluoroethylene block or a modified polytetrafluoroethylene block subjected to a thermal fusion treatment under reduced pressure or subjected to a pressurized thermal fusion treatment after being subjected to fusion under reduced pressure.

TECHNICAL FIELD

The present invention relates to a method for producing apolytetrafluoroethylene film suited as a covering film to be attached ona gasket of a syringe barrel that is used for administering a drugliquid to a human body or an animal in pharmaceutical and medicalfields, or on an inner surface of an insertion bore formed in a top capinto which a tip end part of the syringe barrel for attachment of aneedle is to be inserted, and further to a film produced by the method,and a plug for medical purposes and a pre-filled syringe using the film.

BACKGROUND ART

In pharmaceutical and medical fields, various plugs for medical purposesare used. Hereinafter, the technology concerning such plugs for medicalpurposes will be described with a pre-filled syringe in which such aplug for medical purposes takes a particularly important functionalrole, as an example.

Recently, a so-called pre-filled syringe has become frequently used. Inthe pre-filled syringe, a syringe barrel serving both as an injectioncylinder and a drug liquid container is preliminarily filled with a drugliquid, and the syringe barrel is transported and stored in thecondition that a tip end part to which a needle is to be attached ishermetically sealed with a top cap, and before administration of thedrug liquid, a needle is attached to the tip end part of the syringebarrel from which the top cap has been removed, and then a piston rod(pushing rod) is pushed-in to slide the gasket toward the tip end of thesyringe barrel, and thus the drug liquid in the syringe barrel isadministered.

The pre-filled syringe is featured by the ability to administer acorrect dose of a drug liquid without erroneous use of the drug liquid,non-necessity of a drug liquid transferring operation, and the abilityto prevent microbial contamination of a drug liquid caused by thetransferring operation.

In conventional pre-filled syringes made of resin, the gasket is made ofvulcanized rubber or the like. For ameliorating the “poor slidingproperties” when the rubber gasket slides on the inner surface of thesyringe barrel, it is necessary to apply silicon grease on the surfaceof the gasket or on the inner surface of the syringe barrel, anddecrease in titer due to adsorption of an active ingredient in the drugliquid by the silicon grease, and contamination of the drug liquid bysilicon microparticles in the silicon grease and adverse effect thereofon a human body have been seen as problems. Also, there is a “problemwith regard to a liquid contact surface” because a soluble ingredient inthe rubber can elute into the drug liquid.

For solving these problems, a gasket in which a covering film formed ofa polytetrafluoroethylene (hereinafter, also referred to as “PTFE”) filmis overlaid on the surface of a rubber gasket body has been developed.In such a gasket, the covering film formed of a PTFE film allowsimprovement in sliding properties of the gasket relative to the syringebarrel, and the like without use of silicon grease.

Here, as a method for producing a PTFE film which is to be a coveringfilm, the following two methods are known: (1) following thermalpressure bonding of a laminate of at least two skived films obtained bycutting (skiving) a PTFE pressure-molded product, a thermal fusiontreatment is conducted at a temperature higher than or equal to themelting point of PTFE to form a film (e.g., see Patent Literature 1),and (2) using a suspension containing PTFE resin powder, a dispersingagent, and a solvent as a material, a PTFE cast film having a centerline mean roughness Ra of surface of 0.05 μm or less and a coefficientof kinetic friction of 0.2 or less is produced by a casting method(e.g., see Patent Literature 2).

By covering the surface of a gasket body with a covering film formed ofa PTFE film produced by the foregoing methods, it is possible to improvethe sliding properties of the gasket relative to the syringe barrel asdescribed above, and to eliminate the need of applying silicon grease onthe inner surface of the syringe barrel, thereby avoiding theaforementioned problems caused by the silicon grease.

Further, since the covering film is configured to be substantially watervapor impermeable by eliminating almost all of fine pinholes and fusiondefective parts, it is possible to prevent a rubber ingredient (solubleingredient) of the gasket body from leaching into the drug tocontaminate the drug liquid. Therefore, the covering film can exert theaforementioned effect by being overlaid not only on the gasket forsyringe where sliding properties are regarded as the most importantproperties, but also on a liquid contact inner surface of an insertionbore of a top cap for syringe into which a tip end part of the syringebarrel is to be inserted, or on a liquid contact surface of an insertionportion of a laminate rubber plug for vial, for its water vaporimpermeability and barrier properties against a leached ingredient asdescribed above.

CITATION LIST Patent Literature

-   [PTL 1] Japanese Laid-Open Patent Publication No. 6-287540-   [PTL 2] Japanese Laid-Open Patent Publication No. 10-314305

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

The conventional methods for producing a PTFE film has a problem ofdifficulty in efficiently and economically producing a PTFE film suitedas a covering film. To be more specific, although a skived film obtainedby cutting a block-shaped PTFE pressure-molded product allows efficientmass production of PTFE film at relatively low cost, the pressure-moldedproduct formed by pressure molding of PTFE powder is a cluster of porousaggregates, and interspaces (interconnected cells) communicating witheach other between PTFE powder particles forming the aggregates or alongcontact interfaces of neighboring aggregates in a weaving manner run allover the pressure-molded product in the form of a network. When such aporous pressure-molded product including interconnected cells issubjected to a thermal fusion treatment under normal pressure, thetemperature of the block-shaped PTFE product subjected to the thermalfusion treatment rises from the superficial side, and contact interfacesof aggregates on the superficial side start fusing in first, and thefused area spreads, and eventually the entire surface of the superficialpart is fused and the outlets of the interconnected cells are blockedand the gas is confined inside. This also applies to an aggregatewherein fusion starts on the superficial side previous to the inside,and the ambient gas is confined inside in the same manner. As a result,no matter if the temperature or the duration of the thermal fusiontreatment is elevated or extended later, the confined gas will not bedissolved into the product subjected to the thermal fusion treatment,and will remain as closed cells. Hence, a skived film obtained bycutting such a product subjected to the thermal fusion treatmentincludes an infinite number of fine pinholes and fusion defective parts.

For making such a skived film into a covering film that is impermeableto water vapor, it is necessary to stack and integrate at least twoskived films so that these fine pinholes and fusion defective parts areout of alignment as is in the forgoing former method. However, thismethod has a problem that process management and quality control arecomplicated because entirely new steps “stacking of films”, “thermalpressure bonding”, and “re-thermal fusion treatment” are added in order,compared to the case where a PTFE film is produced just by skiving.

Even if continuity of fine pinholes or fusion defective parts is brokenby sticking a plurality of porous skived films together, an infinitenumber of pinholes still remain in the superficial skived film althoughthe pinholes do not penetrate to the surface of the opposite side. Whenresin which is to become a plug body is injection molded for stickingthe skived films on a sliding surface or a liquid contact surface of theplug body, the skived film may tear from one of the infinite number ofpinholes as an origin due to impact elongation exerted on the skivedfilms. This deteriorates the yield of molding.

On the other hand, in the latter method, the thickness of a PTFE filmobtained by a single application is very small, and a film having auniform thickness cannot be obtained unless the thickness of the film isgradually increased by repeating a series of steps of “application ofPITFE suspension”, “drying”, and “thermal fusion treatment” forobtaining a film having a thickness of about 20 μm to 150 μm which isparticularly suited as a covering film. Therefore, the productionefficiency is very poor, and there is a problem of difficulty ineconomically producing a PTFE cast film suited as a covering film.

Additionally, since a PTFE suspension is used for application, aninfinite number of pinholes occur in the dry film as the suspensiongradually gets dry, and the pinholes remain even after the dry film issubjected to a thermal fusion treatment. Then, films are piled up byrepeated application, drying, and a thermal fusion treatment, andpinholes occurring in the respective films are out of alignment and donot communicate with each other. Therefore, a PTFE cast film havingexcellent water impermeability and barrier properties comparable withthose described above is formed. However, since pinholes appear in filmsof front and back superficial layers, tear can be caused from one ofthese pinholes as an origin, during injection as described above.

Therefore, it is a primary object of the present invention to provide aPTFE skived film capable of exhibiting, with a single layer, slidingproperties, barrier properties relative to a liquid contact surface, andexcellent tear resistance during injection molding which are theaforementioned problems, and a method for producing the film. It is asecondary object of the present invention to provide a plug for medicalpurposes and a pre-filled syringe produced efficiently and economicallyby using the PTFE film produced by said method.

Solution to the Problems

A first aspect is characterized by “a skived film for covering a surfaceof a plug for medical purposes obtained by cutting apolytetrafluoroethylene block or a modified polytetrafluoroethyleneblock subjected to a thermal fusion treatment under reduced pressure orsubjected to a pressurized thermal fusion treatment after beingsubjected to fusion under reduced pressure”, and a second aspect ischaracterized in that “tensile elongation in a machine direction whichis a longitudinal direction of the film is greater than or equal to500%”.

A conventional skived film can hardly be used for covering a surface ofa plug for medical purposes because it includes an infinite number ofpinholes and fusion defective parts as described above, and has “watervapor impermeability” much lower than that required for medicalpurposes. In contrast, as will be described later, the film obtained bycutting a product subjected to a “thermal fusion treatment under reducedpressure”, or “pressurized thermal fusion treatment after beingsubjected to fusion under reduced pressure” includes no fine pinholesand fusion defective parts, and satisfies the water vapor impermeability(amount of water vapor transmission is measured for determination)required for covering surface of a plug for medical purposes, so that itfirst finds application as a film for covering a surface of a plug formedical purposes. Also when “tensile elongation in a machine directionwhich is a longitudinal direction of the film is greater than or equalto 500%”, impact elongation in covering an elastomer for a plug bodyduring the injection molding step is overcome and the film will nottear, so that it is possible to realize such high yield in injectionmolding that cannot be achieved by a cast film or by a conventionalskived film. Since the skived film is stretched in the longitudinaldirection when it is passed through rollers under tension for removingthe undesired curling, elongation is smaller in the longitudinaldirection than that in the width direction. Therefore, elongation occursin the machine direction which is a longitudinal direction.

In a plug for medical purposes described in a third aspect, for example,a gasket for syringe, an intermediate gasket for syringe, a top cap forsyringe, or a laminate plug for vial as described in a fourth aspect, ora pre-filled syringe described in a fifth aspect, since the skived filmaccording to the first or second aspect is overlaid on the superficialsurface, or at least on the sliding surface or the liquid surface of theplug body made of elastomer, it is possible to realize smooth movementof a piston, and to block elution of an inhibitor from the elastomer onthe body side to the drug liquid side in the liquid contact part, and toblock water diffusion from the charged drug liquid by exertion of“sliding properties”, “barrier properties”, and “water vaporimpermeability”.

According to a sixth aspect, a method for producing apolytetrafluoroethylene film for covering a surface of a plug formedical purposes (first method) is characterized by the steps of“pressure-molding powder material of polytetrafluoroethylene or modifiedpolytetrafluoroethylene charged in a mold to obtain a pressure-moldedproduct having interconnected cells inside; subjecting thepressure-molded product obtained by the pressure molding to a thermalfusion treatment under reduced pressure; and cutting the productsubjected to the thermal fusion treatment obtained by the thermal fusiontreatment to obtain a film”.

Here, “subjecting the pressure-molded product obtained by the pressuremolding to a thermal fusion treatment under reduced pressure” means thatthe ambient pressure has reached (or almost reached) a reduced pressurecondition before “heating” the pressure-molded product for “fusiontreatment” as will be described in detail later. And this “reducedpressure condition” is kept until at least the entire superficialsurface of the pressure-molded product is baked into the state includingpractically no pinhole (the entirety is covered with a skin). By keepingthe reduced pressure until the superficial surface is baked to the stateincluding practically no pinhole, the pressure-molded product is bakedto the state where no pinholes are included up to the core by preventingthe external air from entering the pressure-molded product undergoingthermal fusion even if the ambient pressure is returned to normalpressure later. Of course, pressure reduction may be continued untilthermal fusion completes or cooling completes.

Next, the “fusion treatment” will be described. PTFE powder charged in amold is pressure-molded to form a pressure-molded product, and thepressure-molded product is a block of a predetermined shape formed byassembly of aggregates which are clusters of fine powder particles.

As is described in the section of PROBLEM, an aggregate is made up offine powder particles which are in contact with each other, and is aporous aggregate in which networks of fine communication holes run. Alsoin a pressure-molded product which is a cluster of the aggregates, theparts that cannot properly come into contact with each other in thevicinity of contact interfaces between aggregates form coarseinterspaces (interconnected cells), and networks of these coarseinterconnected cells run throughout the interior of the pressure-moldedproduct as is the same with the above. Therefore, it is doubly porous.

By reducing the pressure to a predetermined pressure before startingheating of the “fusion treatment”, not only the coarse interspaces(interconnected cells) remaining between aggregates as described aboveare drawn outside, but also the gas having entered inside theinterconnected cells during the compression molding is drawn outsidefrom the fine interconnected cells remaining in the aggregates(degassed), so that the interior has the same (almost the same) reducedpressure condition as that of the ambient environment.

When “heating” for the “fusion treatment” is started in this condition,contact interface between neighboring aggregates softens by the heat andfusion gradually progresses from the superficial side of thepressure-molded product toward the interior. At the same time, also inthe aggregates residing in the superficial part of the pressure-moldedproduct, softening and fusion gradually progress from the superficialside. As a result, softening and fusion progress even in the aggregatesresiding on the superficial side of the pressure-molded product, priorto the interior. Therefore, bubbles that have turned into closed cellsfrom the interconnected cells because of closure of the outlets are leftinside.

In association with progression of thermal fusion (or temperatureelevation or keeping of fusion temperature), the fused area graduallyextends due to reduction in surface tension at contact interface, andthe closed cells are reduced. At this time, since the internal pressureof the closed cells is reduced and there is little gas in the interior,and there is no resistance that interferes extension of fusion, theclosed cells can be reduced to the minimum, and occurrence of finepinholes and fusion defective parts inevitably accompanying a powderthermal fusion treatment is greatly controlled. Such fusion also occursinside aggregates as well, and substantially complete fusion is achievedin the entire product subjected to the thermal fusion treatment. And atthe time when fusion has progressed to the core, the “fusion treatment”completes and cooling follows.

By producing a film by cutting a product subjected to the thermal fusiontreatment obtained by such a thermal fusion treatment method, it ispossible to obtain a PTFE film including least fine pinholes and fusiondefective parts, that is substantially water vapor impermeable andsuited as a covering film.

A seventh aspect is further improvement of the sixth aspect (secondmethod), and characterized by the steps of “pressure-molding powdermaterial of polytetrafluoroethylene or modified polytetrafluoroethylenecharged in a mold to obtain a pressure-molded product havinginterconnected cells inside; subjecting the pressure-molded product to aprimary thermal fusion treatment under reduced pressure to block outletsof communication holes of the pressure-molded product to obtain aproduct subjected to the primary thermal fusion treatment including onlyclosed cells remaining inside; subjecting the product subjected to theprimary thermal fusion treatment to a secondary thermal fusion treatmentunder increased pressure to obtain a product subjected to the secondarythermal fusion treatment from which the closed cells have disappeared;and cutting the product subjected to the secondary thermal fusiontreatment to obtain a film”.

Also in this case, the “primary thermal fusion treatment” is started inthe condition that the pressure is reduced to an approximatelypredetermined pressure. And, the product subjected to the primarythermal fusion treatment in which apertures of fine communication holesin aggregates located in the superficial part of the pressure-moldedproduct or coarse communication holes between aggregates are closed andonly closed cells having reduced internal pressure remain as a result ofthe primary thermal fusion treatment, is subjected to the secondarythermal fusion treatment under increased pressure. Since the entiresuperficial surface of the product subjected to the primary thermalfusion treatment is covered with a skin, the pressure is applied on theentire superficial surface of the product subjected to the primarythermal fusion treatment, and the entirety is pressed toward the center,and the closed cells gradually disappear by this pressurization forcewithout any resistance.

In the first method not employing “pressurization”, fusion progressesonly by reduction in surface tension at contact interface “duringfusion”. When the closed cells gradually contract to become very finepinholes, such fine pinholes are physically crushed by “pressurization”although they are difficult to be eliminated only by reduction insurface tension. Hence, the product subjected to the secondary thermalfusion treatment is much denser than the product subjected to thethermal fusion treatment produced by the first method. By preparing afilm by cutting the product subjected to the secondary thermal fusiontreatment obtained in such a manner, it is possible to obtain a PTFEfilm that includes lesser fine pinholes and fusion defective parts, andis more impermeable to water vapor and more desirable as a covering filmthan the film formed in the invention described in the sixth aspect.Shifting from the primary thermal fusion treatment to the secondarythermal fusion treatment may be conducted continuously using the samethermal fusion treatment furnace, or the treatments may be conducted ina batch manner using different thermal fusion treatment furnaces.

Powder material of PTFE used herein is powder of solely PTFE, andmodified PTFE is PTFE that is modified for adaptation to the use. In thepresent invention, elongation is an important factor as will bedescribed later, and hence, modified PTFE in which priority is given toelongation, for example, a polymer of tetraftluoroethylene obtained bycopolymerizing 0.01 to 1 part by weight of alkylvinylether having one tofour carbon atoms in a perfluoroalkyl chain with 100 parts by weight ofPTFE is recited as an example.

Here, the pressure in reducing the pressure during the thermal fusiontreatment (or the primary thermal fusion treatment) preferably fallswithin the range of 0.013 to 133 Pa. When the pressure (reducedpressure) during the thermal fusion treatment is higher than 133 Pa (orthe degree of vacuum is lower than the predetermined range), degassingof the gas having entered interspaces between neighboring PTFEaggregates as well as in fine pinholes in PTFE aggregates isinsufficient, and the gas is confined inside during the thermal fusiontreatment, so that fine pinholes and fusion defective parts remain. Onthe contrary, when the pressure is lower than 0.013 Pa (or the degree ofvacuum is higher than the predetermined range), gas does not remain notonly in interspaces between neighboring PTFE aggregates but also in finepinholes in PTFE aggregates, however, massive equipment is required forgenerating vacuum and it is no longer possible to efficiently andeconomically obtain the product subjected to the thermal fusiontreatment (or product subjected to the primary thermal fusiontreatment). In short, the reduced pressure is selected so that finepinholes and fusion defective parts will not remain in the productsubjected to the thermal fusion treatment (or the product subjected tothe primary thermal fusion treatment).

An eighth aspect is characterized in that “the powder material ofpolytetrafluoroethylene or modified polytetrafluoroethylene charged inthe mold is pressure-molded under reduced pressure to obtain apressure-molded product” in the sixth and seventh aspects, and accordingto this, it is possible to obtain a pressure-molded product having amuch higher density than that obtained by pressure-molding at normaltemperature.

In the method for producing a polytetrafluoroethylene film, it ispreferred that “a thermal fusion treatment temperature (or primary,secondary thermal fusion treatment temperature) is 320 to 400° C.”.Since the melting point of PTFE is approximately 327° C. (gelationoccurs and mechanical properties rapidly change at temperatures higherthan this), a longer time is required for the thermal fusion treatmentwhen the temperature during the thermal fusion treatment is less than320° C. On the contrary, since the temperature at which PTFE startsdecomposing is approximately 390° C., decomposition starts and gasbubbles occur inside the fused product when the temperature during thethermal fusion treatment exceeds 400° C. In view of the melting point ofPTFE, the temperature is more preferably 350 to 370° C. at which fusioneasily progresses, and within this temperature range, the shape will notbe lost upon heating at a temperature exceeding the melting point, andthe shape will be restored without deterioration upon returning tonormal temperature.

The pressurization pressure during the secondary thermal fusiontreatment is higher than or equal to 0.2 MPa. Generally, when thethermal fusion treatment temperature is low, the pressurization pressureis set high, and when the thermal fusion treatment temperature is high,the pressurization pressure is set low. Of course, when both of theseare set high, the thermal fusion treatment is accelerated. When thepressure is lower than 0.2 MPa, the method does not differ from thefirst method. The higher the pressurization force, the more the tensileelongation (%) and the amount of water vapor transmission are improved,however, pressurization at 5 MPa or higher is not economical because anextra cost is required for the pressure resistant structure of thepressurized heating furnace. Therefore, the upper limit is practically 5MPa.

While the shape of the product subjected to the thermal fusion treatment(or the product subjected to the secondary thermal fusion treatment) isnot specified, it is preferably “a rectangular parallelepiped or a cube”or “a circular column or a cylinder”. In the case of a cylinder, inparticular, fusion progresses both from the superficial side and theinner side, and fusion progresses rapidly and completely to the core. Inthe case of “a rectangular parallelepiped or a cube”, a film of arequired size can be obtained by planing, and in the case of “a circularcolumn or a cylinder”, a long PTFE film can be produced efficiently andeconomically by passing a mandrel in the center, and cutting the productsubjected to the thermal fusion treatment (or the product subjected tothe secondary thermal fusion treatment) while it is rotatedcircumferentially about the mandrel.

It is preferred that “the film obtained by cutting the product subjectedto the thermal fusion treatment (or the product subjected to thesecondary thermal fusion treatment) has a thickness ranging from 20 to150 μm”. A film having large thickness is used for deep drawing.

Here, “elastomer” is a generic name for materials having rubber-likeelasticity, and includes both “thermosetting elastomer” generally called“rubber” having relatively high heat resistance that will not softenupon application of heat such as vulcanized rubber and thermosettingresin elastomer, and “thermoplastic elastomer” that will soften toexhibit fluidity upon application of heat, and return to a rubber-likeelastic body upon cooling, and can be rapidly formed by injectionmolding.

Examples of the “drug container” include “syringe” and “vial”. Specificexamples of the “plug for medical purposes” include a gasket forsyringe, an intermediate gasket for syringe, a top cap for syringe, anda laminate plug for vial (the fourth aspect).

The invention described in the fifth aspect of the present invention isa pre-filled syringe featured in that “the syringe barrel 4 charged withthe drug liquid 7 is hermetically sealed with the gasket for syringe 1and the top cap for syringe 6 as exemplified in the fourth aspect”.

Advantageous Effects of the Invention

According to the present invention, by developing a novel skived methodand employing the same, application of a skived film as a covering filmfor a plug for medical purposes, that has been conventionally consideredto be impossible, is enabled. As a result, it becomes possible toefficiently and economically provide a plug for medical purposes such asa gasket for syringe and a pre-filled syringe by using the PTFE filmproduced by this method.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view showing one example of a pre-filledsyringe to which the present invention is applied.

FIG. 2 is a cross-sectional view showing another example of thepre-filled syringe to which the present invention is applied.

FIG. 3 is a graph for comparing results of a water vapor transmissiontest for skived films prepared by a normal pressure fusion method andthe first and second methods of the present invention.

FIG. 4 is a cross-sectional view of major part showing one example of amethod for attaching a film to a gasket body in a stretched manner.

DESCRIPTION OF EMBODIMENTS

Hereinafter, for example, a pre-filled syringe (of course the one towhich the PTFE skived film of the present invention is applied, but notlimited to a pre-filled syringe) to which the present invention isapplied, and a PTFE skived film used in the pre-filled syringe will bedescribed with reference to the drawings. FIG. 1 is a cross-sectionalview showing one example of a pre-filled syringe A (of the presentinvention) to which a gasket for syringe 1 and a top cap for syringe 6which are plugs for medical purposes of the present invention areapplied.

As shown in FIG. 1, the pre-filled syringe A of the present inventiongenerally includes the gasket for syringe 1 (hereinafter, also referredto simply as “gasket 1”), a syringe barrel 4, a piston rod 5, and thetop cap for syringe 6 (hereinafter, also referred to simply as “top cap6”). Reference numeral 7 in FIG. 1 denotes a drug liquid (injectionliquid) charged in the syringe barrel 4.

As shown in the enlarged view of FIG. 1, the gasket 1 includes a gasketbody 2, and a skived film 3 for covering formed of apolytetrafluoroethylene (PTFE) film overlaid to entirely cover a slidingsurface relative to the inner surface of the syringe barrel 4, and aliquid contact surface in the gasket body 2.

The gasket body 2 is an approximately circular columnar member (namely,plug body) formed of elastomer, having a diameter of the center partslightly smaller than diameters of the lateral sides, and is provided inits bottom surface (surface on the side to which the piston rod 5 isattached) with a female screw portion 8 for connecting the piston rod 5.

The “elastomer” forming the gasket body 2 includes both “thermosettingelastomer”, such as vulcanized rubber and thermosetting resin elastomer,and “thermoplastic elastomer” as described above.

Examples of the vulcanized rubber include butyl rubber, SUR(styrene-butadiene rubber), EPR (ethylene-propylene rubber), EPDM(ethylene-propylene-diene rubber), NBR (acrylonitrile butadiene rubber),NR (natural rubber), IR (isoprene rubber), CR (chloroprene rubber), IIR(butyl rubber), chlorinated butyl rubber, and brominated butyl rubber,and examples of the thermosetting resin elastomer include fluorinerubber and silicone rubber.

Examples of the thermoplastic elastomer include SBS(styrene-butadiene-styrene block copolymer), SEBS(styrene-ethylene-butadiene-styrene block copolymer), EP(ethylene-propylene copolymer), PA (polyamide), and polyurethane.

The covering film 3 is formed of the PTFE film obtained by the skivedmethod according to the present invention, and contains in the entirefilm, almost no fine pinholes which are residues of interspaces betweenaggregates and fine pinholes included in the aggregates, as well asporous aggregates that are observed in the state of the pressure-moldedproduct (see the result of the water vapor transmission test in Table 1and FIG. 3). Although tensile elongation (%) differs in the longitudinaldirection (machine direction) and in the width direction (crossdirection) of the film as described above, the film has enoughresistance to later-described impact elongation to endure impactelongation during injection of the gasket body 2 even in thelongitudinal direction of the film in which tensile elongation (%) issmaller (see results of elongation test in Table 1), and tear of thefilm during injection is hardly observed. The surface of the PTFE filmobtained by the skived method according to the present invention has aninfinite number of very shallow parallel knife cuts that are formedduring cutting in the longitudinal direction of the film, however, sincethe infinite number of very shallow knife cuts run in the longitudinaldirection of the film having smaller tensile elongation (%), the knifecuts will not become an origin of tear during injection molding, andthere is no pit (hole) in the surface that is to become an origin oftear inevitable for a cast film.

The skived film as described above is overlaid to entirely cover thesliding surface relative to the inner surface of the syringe barrel 4(in other words, outer circumferential face of the gasket body 2) andthe tip end surface which is a liquid contact surface in the gasket body2, to impart high sliding properties to the sliding surface of thegasket body 2, and barriers properties of inhibiting transfer of awater-soluble impurity into the drug liquid from the gasket body 2 andwater vapor impermeability of preventing evaporation of water from thecharged drug.

Preferably, the thickness of the PTFE film forming the covering film 3,before being overlaid on the gasket body 2, ranges from 20 μm to 150 μm,inclusive. The film thickness is selected depending on the shape of thematerial to be laminated, in particular, depending on the deep drawingamount. A thicker film is used for a deeper drawing amount.

Since the syringe barrel 4 has many variations from a small-sized onehaving a small inner diameter (for example, an inner diameter of 4.65mm) to a large-sized one having a large diameter (for example, an innerdiameter of 50 mm) for imaging, the gasket 1 itself also hascorresponding variations from one having a small diameter to one havinga large diameter, and also the film thickness of the covering film 3used herein is selected depending on the shape and the depth of drawing.

Lamination of the covering film 3 onto the gasket body 2 is achieved byinjection molding carried out in the following manner. The covering film3 is stretched on a female mold in which the shape of the gasket isengraved, then a male mold having a male screw portion 9 formed in aprotruding manner for screw attachment of a piston rod is set to pushthe covering film 3 into the bore for forming a gasket in the femalemold, and an elastomer which is to become the gasket body 2 is chargedat high speed by being injected at high pressure between the pushed-incovering film 3 and the male screw portion 9 (see FIG. 4).

In such injection molding, the covering film 3 is rapidly stretched inthe machine direction and the cross direction of the film by injectionof the elastomer at high pressure, and elongation is a very importantfactor in mass production because poor elongation may cause tear. Athick film is used for deep drawing because it allows large elongation.At the same time, it is also important to improve the elongation of thecovering film 3 for enduring injection at high pressure as is alreadydescribed, and for this, it is more preferred to produce and use, inplace of the PTFE film, a modified PTFE film by using modified PTFE (forexample, a polymer of tetrafluoroethylene obtained by copolymerizing0.01 to 1 part by weight of alkylvinyl ether having 1 to 4 carbon atomsin a perfluoroalkyl chain with 100 parts by weight of PTFE) as powdermaterial.

Regarding the elongations of these films (in particular, modified PTFEfilm), these films preferably exhibit tensile elongation (more strictly,fracture elongation) of at least 500% or greater in the machinedirection in which the film is weak (As described above, since theskived film is passed between multi-stage rollers under tension in thelongitudinal direction for eliminating waving of the film after beingformed into a film by cutting, the film is stretched in the longitudinaldirection of the film and thus has higher tensile strength in thelongitudinal direction than in the width direction, but elongation inthe longitudinal direction is deteriorated in comparison with that inthe width direction.). The tensile elongation in the longitudinaldirection of the sample shown in Table 1 that is likely to cause tear offilm during injection molding (Unmodified/Comparative 1 (Comparativeexample: Film fused at atmospheric pressure without pressure reductionand pressurization, using unmodified material)) is 450%.

With the elongation in the machine direction of less than or equal to500%, the PTFE film may tear depending on the shape of the gasket 1during stretching in injection molding of the gasket 1. While an upperlimit of elongation is not limited, excessive elongation makes the filmtoo soft to impair not only sliding properties but also shape retentionof the gasket 1, although large elongation will not inhibit resilienceof the gasket body 2. From this point of view, preferably, an upperlimit of elongation is practically 650% or 700%. Thus, the thickness ofthe PTFE film or the modified PTFE film overlaid on the gasket body 2 byinjection is 10 μm to 20 μm. And knife cuts in the shapes of fineprojecting and recessed lines generated by cutting are significantlylessened to such a degree that they will disappear by the greatelongation during injection molding as described above. An adhesionsurface of the covering film 3 with regard to the gasket body 2 issubjected to an adhesiveness improving treatment as will be describedlater for enhancing adhesiveness.

The method for producing a PTFE skived film that forms the covering film3 described hereinafter is an improved method based on a conventionalskived method. Specifically, first, powder material (so-called moldingpowder) of polytetrafluoroethylene (PTFE) or modified PTFE is charged ina mold, and compressed at room temperature, under a pressure of 10 to 50MPa to form a circular columnar or cylindrical product. The pressure atthe time of compression is limited in the above range because when thepressure is lower than 10 MPa, mechanical strength of the obtainedpressure-molded product is poor, and the handling such as transfer tothe subsequent step becomes difficult, and a lot of air remain insidethe pressure-molded product, so that fine pinholes and fusion defectiveparts frequently occur in the obtained film when the pressure-moldedproduct is finally processed into a film. When the pressure is higherthan 50 MPa, the mechanical strength of the pressure-molded product isimproved, but the problem of fine pinholes or fusion defective parts inthe obtained film remains unsolved, and the properties of the film arenot so improved although the massive equipment for pressurization isused. (Here, the pressure-molded product can be further densitfied byemploying pressure reduction together with compression underpressurization. The pressure reduction may be employed after compressionmolding under pressurization. When the reduced pressure condition can bemaintained continuously to the subsequent fusion treatment, it isconvenient to shift to the fusion treatment while keeping the reducedpressure condition to avoid the need of reducing the pressure again inthe fusion treatment.) This point also applies to the second method. Thedegree of pressure reduction is preferably 0.013 to 133 Pa foradaptation to the subsequent step.

The shape of the pressure-molded product is not particularly limited,and an optimum shape such as a circular column, a cylinder, arectangular parallelepiped or a cube is selected depending on the methodfor forming a film from the product subjected to the thermal fusiontreatment and on the thermal fusion treatment condition. Thepressure-molded product is a cluster of aggregates of PTFE powdermaterial or modified PTFE powder material because it is formed just bycompression under pressurization. Therefore, there are an infinitenumber of interspaces of various sizes between neighboring powderparticles or between neighboring aggregates although powder particlesinside each aggregate adhere tightly to each other, and the aggregatesadhere tightly to each other at their contact interface. The interspacescommunicate with each other to give a network of fine communicationholes throughout the pressure-molded product, so that thepressure-molded product is porous. When the pressure-molded product isput in a reduced pressure condition, and this condition is notmaintained, these communication holes are filled with gas in the ambientenvironment (normally air).

Then, the pressure-molded product formed in an atmospheric pressure isput into a heating furnace, and the internal pressure of the heatingfurnace is reduced to a degree of vacuum of 0.013 to 133 Pa, and theinterior of the pressure-molded product accommodated in the furnace isalso made to have the same degree of vacuum to remove the gas from theinterspaces (communication holes). Typically used degree of vacuumranges from 0.13 Pa to 13.3 Pa. After conducting the thermal fusiontreatment as described above, normally at 320 to 400° C. (morepreferably 350 to 370° C.) for several to several ten hours, dependingon the size and the shape of the pressure-molded product while keepingthis reduced pressure condition, the pressure-molded product is cooledto obtain a product subjected to the thermal fusion treatment.

In the pressure-molded product undergoing the thermal fusion treatment,since the temperature rises from the superficial side, and the heat isconducted toward the center part, fusion of PTFE aggregate itself andfusion at contact interfaces between aggregates progress from thesuperficial side in an early stage of the thermal fusion treatment inthe porous pressure-molded product, and the aforementioned interspacesgradually disappear. On the other hand, inside the aggregates themselvesand inside the pressure-molded product which is a cluster of theaggregates, fusion at contact interface is delayed, and interspaces areconfined inside because temperature rise is delayed. In other words,outlets of interconnected cells are blocked to give closed cells.

However, fusion at contact interface is not interfered because there islittle gas inside the interspaces (closed cells), and disappearance ofinterspaces (closed cells) up to the core of the pressure-molded productis eventually achieved. By securing a sufficient thermal fusiontreatment time, fusion at contact interface completely progresses, andelimination of fusion defective parts due to defective fusion is alsoachieved. Therefore, an estimated duration and heating temperature ofthe thermal fusion treatment is the time required for fine pinholes andfusion defective parts inside the product subjected to the thermalfusion treatment to disappear, from the purpose of producing a PTFE filmwith no fine pinholes, which is an object of the present invention.

Here, the pressure reduction range in reducing the internal pressure ofthe heating furnace during the thermal fusion treatment is preferably0.013 to 133 Pa as described above. Further, the temperature during thethermal fusion treatment is preferably in the range from 320 to 400° C.(more preferably 350 to 370° C.) as described above. Technicalsignificances of the pressure range and the temperature during thethermal fusion treatment are as described above. As an indication forthe thermal fusion treatment, although fusion is expected to progressesto the core typically in about five hours after the temperature hasreached a predetermined temperature (360° C.) for a circular columnarproduct having an outer diameter of 100 mm, an inner diameter of 20 mm,and a thickness of 40 mm, heating is conducted for about ten hours forsafety and then cooling by allowing to cool follows.

As another method for obtaining a product subjected to the thermalfusion treatment (second method), the following method may be employed.Specifically, similarly to the first method, powder material ofpolytetrafluoroethylene or modified polytetrafluoroethylene is chargedin a mold, and pressure-molded under normal pressure or reduced pressureto obtain a pressure-molded product. The pressure molding and the formedshape are as same as those in the first method.

Then, the pressure-molded product is subjected to a primary thermalfusion treatment under reduced pressure. The condition of the thermalfusion treatment is as described above, and interspaces (interconnectedcells) are blocked from the superficial side of the pressure-moldedproduct. In this case, an estimated duration of the primary thermalfusion treatment is the time required for communication holes in theentire surface on the superficial side of the product subjected to theprimary thermal fusion treatment to disappear to give the condition thatonly closed cells remain inside. The thermal fusion treatmenttemperature is as same as that in the first method.

After conducting the primary thermal fusion treatment, the productsubjected to the primary thermal fusion treatment is subjected to asecondary thermal fusion treatment unwder increased pressure bypressurizing the interior of the same heating furnace to a predeterminedpressure, or by taking out the product subjected to the primary thermalfusion treatment and transferring it to another heating furnace, andpressurizing the interior of the heating furnace to a predeterminedpressure.

The secondary thermal fusion treatment is conducted under increasedpressure because the entire surface of the superficial part of theproduct subjected to the primary thermal fusion treatment is fused, andthe pressurization force in the thermal fusion treatment furnace isexerted toward the center from the entire superficial surface of theproduct subjected to the primary thermal fusion treatment, to crush theclosed cells remaining inside under reduced pressure. At the same time,contact interface of powder particles forming PTFE aggregates themselvesthat are physically in contact with each other, and contact interface ofthe aggregates are fused by the heat transferred from the superficialside, and almost all of the remaining fine pinholes and fusion defectiveparts are eliminated. In the second method, since the secondary thermalfusion treatment is conducted under increased pressure, elimination offine pinholes and fusion defective parts is achieved more completely upto the core. The thermal fusion treatment temperature is as same as thatin the primary thermal fusion treatment.

The pressurization pressure in the secondary thermal fusion treatment ishigher than or equal to 0.2 MPa (practically, the upper limit is 5 MPaas described above). Normally, the pressurization pressure is raisedwhen the thermal fusion treatment temperature is low, and thepressurization pressure is lowered when the thermal fusion treatmenttemperature is high. For shortening the fusion time, the temperature andthe pressure are raised. The technical significance of thepressurization range is as already described. A practical pressurizationrange is 0.7 to 0.9 MPa.

Then, the product subjected to the thermal fusion treatment obtained bythe first method or the product subjected to the secondary thermalfusion treatment obtained by the second method is set, for example, on alathe machine while a mandrel is passed through the center hole thereofwhen the product is of a cylindrical shape, and rotatedcircumferentially, and in this condition, a cutting tool such asmetallic knife is pushed at a specific angle at a specific pressure tocut the product to obtain a PTFE film of 20 to 150 μm thick. When theproduct subjected to the thermal fusion treatment or the productsubjected to the secondary thermal fusion treatment is a cylindricalsolid, after cutting out the center part of the product, a mandrel ispassed therethrough as described above, or press-fitted therein, andthen the product is subjected to cutting. When the product is arectangular parallelepiped or a cube, a PTFE film is obtained by amethod like planing. The obtained film is passed through rollers underheating to remove the undesired curling occurring by cutting (rotarycutting). As a result, the film is stretched and has slightly highertensile strength in the rolling direction (or the longitudinal directionof the film or the machine direction) than in the width direction (crossdirection), while on the other hand, it has smaller elongation in themachine direction than in the cross direction.

In the film obtained in this manner, PTFE powder particles in aggregatesthemselves and neighboring aggregates are fused and integrated in aseamless manner as if rice cakes were fused, and very little finepinholes and fusion defective parts that may cause tear of the filmduring injection molding are included in the superficial surface,although the superior surface includes microscopic knife cuts in thelongitudinal direction of the film. Therefore, it becomes possible toefficiently and economically produce a PTFE film that is substantiallyimpermeable to water vapor and is desirable as a covering film. Asdescribed above, microscopic knife cuts are not disadvantageous ininjection molding.

The PTFE film produced in the manner as described above has essentiallypoor adhesiveness, and is disadvantageous in that the joining strengthwith the gasket body 2 is very weak. For this reason, it is necessary toapply an “adhesiveness improving treatment” on the joint surface betweenthe PTFE film and the gasket body 2. In the present embodiment, the“adhesiveness improving treatment” is conducted by providing the jointsurface between the PTFE film and the gasket body 2 with a silicamicroparticle layer made up of a binder and silica (SiO₂) microparticles(not shown), to allow secure joining between the PTFE film having pooradhesiveness and the gasket body 2 mainly by the anchoring effect. Ofcourse, as the “adhesiveness improving treatment”, other methods such asa chemical treatment with metallic sodium or a plasma treatment in anargon atmosphere may be conducted in place of the above method. In FIG.4( a), the surface subjected to the adhesiveness improving treatment ofthe PTFE skived film 3 is denoted by 22, and the surface not subjectedto the treatment is denoted by 20.

The syringe barrel 4 is formed with a needle attachment part 4 a in itstip end, a finger hook part 4 b in its rear end, and a cylindrical drugliquid packing part 4 c therebetween, and is made of cyclic polyolefinin this embodiment. Of course, the shape of the syringe barrel 4 is notlimited to the depicted one, and the syringe barrel 4 may be made ofpolypropylene, glass, or the like.

The piston rod 5 is a rod-like member having a gasket attachment part 5a in its tip end part, and a finger rest part 5 b in its rear end. Theouter circumference of the gasket attachment part 5 a of the piston rod5 is engraved with a male screw to be screwed with the female screwportion 8 formed by digging the gasket body 2 of the gasket 1 asdescribed above. Also, the piston rod 5 is formed of a resin such ascyclic polyolefin, polycarbonate, or polypropylene, similarly to theaforementioned cylinder 4.

The top cap 6 is a sealing member that is attached to the needleattachment part 4 a of the syringe barrel 4 to prevent the drug liquid 7charged in the syringe barrel 4 from leaking, and to prevent the drugliquid 7 from being contaminated by bacteria and so on suspended in theair. The top cap 6 is made up of an approximately circular columnar capbody (or plug body) 6 a, and the covering film 3 overlaid in the samemanner for the gasket 1, on the surface of a recess part 6 b which isformed concavely on the top face of the cap body 6 a and in which theneedle attachment part 4 a is to be fit. The cap body 6 a is formed ofelastomer similarly to the gasket body 2 described above, and thecovering film 3 is formed of a PTFE film that is formed in the abovemethod similarly to the one covering the gasket body 2.

By overlaying the covering film 3 on the superficial surface of therecess part 6 b of the cap body 6 a in the manner as described above, itis possible to make the needle attachment part 4 a of the syringe barrel4 fit in the recess part 6 b of the top cap 6 smoothly, and to improvethe liquid tightness and air tightness of the top cap 6 formed ofelastomer.

FIG. 2 shows the case where an intermediate gasket 10 for syringe isused, and the intermediate gasket 10 is slidably accommodated in thesyringe barrel 4. In a space 4 d between the needle attachment part 4 aof the syringe barrel 4 and the intermediate gasket 10, a solid agent 7a of, for example, powder of drug is stored, and a space 4 e between theintermediate gasket 10 and the gasket 1 for piston is filled with purewater 7 b. The outer wall of the space 4 d for storage of solid agent isprovided with a bypass canal 4 f formed in the longitudinal direction ofthe syringe barrel 4. As the piston rod 5 is pushed in, the pure water 7b flows into the space 4 d for storage of solid agent through the bypasscanal 4 f when the intermediate gasket 10 moves past an inlet 4 f 1 ofthe bypass canal 4 f, and rapidly dissolves the solid agent 7 a in thespace 4 d for storage of solid agent to give an injection liquid. Inthis case, as shown in the enlarged view of FIG. 2, the PTFE film 13 isattached to the intermediate gasket 10 to cover one end surface 12 a andmost of the circumferential face of the cylindrical gasket body 12, andthe circumferential part is in slidable contact with the inner surfaceof the syringe barrel 4. The intermediate gasket 10 is disposed insidethe syringe barrel 4 so that the end surface 12 a on which the film isattached faces the pure water 7 b. Although not shown in the drawing, agroove may be formed in the longitudinal direction in the inner wall inplace of the external bypass canal 4 f to function as a bypass, oralthough not shown in the drawing, both end surfaces of the intermediategasket 10 and the circumferential face continuing to the both endsurfaces may be covered with the PTFE film 13.

Focusing on the high barrier properties in a liquid contact surface witha drug liquid, the invention can be applied to plugs for medicalpurposes such as plugs of vials typically the gasket for syringe 1 andthe top cap for syringe 6 configured as described above.

(Comparison in time-dependent change between results of a water vaportransmission measurement test for skived films according to the firstand second methods of the present invention and a skived film subjectedto a fusion treatment in atmospheric pressure without pressure reductionaccording to the conventional method: FIG. 3)

The transmission amount and its change of each PTFE film were determinedin conformity with JIS Z-0208 (Testing Methods for Determination of theWater Vapor Transmission Rate of Moisture-proof Packaging Materials(Dish method)). According to FIG. 3, the inclination of the skived film(Sample A) obtained by the first method is smaller than that of theskived film formed by the conventional method (Comparative example), andthe inclination of the skived film obtained by the second method becomesgentler as the pressurization force in the secondary thermal fusiontreatment under increased pressure increases and approximates to that ofa sample (Modified C4). Of course, when the pressuring force exceeds 5.0MPa, the inclination becomes less than that of the sample (Modified C4),and the amount gradually decreases and converges to a certain value inthe vicinity of the amount of the sample. Water vapor transmission rate(mg/m²) per unit area after 24 hours is calculated from this graph andshown as water vapor transmission amount in FIG. 3 (the value obtainedby dividing measurement of the moisture having passing through theskived film and absorbed in calcium chloride (anhydrous) by water vaportransmission area). The first and second skived films of the presentinvention are significantly improved in comparison with the comparativeexample (Unmodified/Comparative 1). As will be described later, thedegree of pressure reduction during the primary thermal fusion is low,and the degree of pressurization during the secondary thermal fusion ishigh.

Table 1 shows comparison of treatment conditions, tensile elongation andtensile strength, water vapor transmission amount, and tear of filmduring injection in these films.

TABLE 1 Water vapor Pressure Fusion Fusion Tensile elongation % Tensilestrength N/mm² transmission Tear of Sample reduction temperature heatingPressurization Machine Cross Machine Cross amount mg/m² film during No.(Pa) (° C.) time (MPa) direction direction direction direction 24 hoursinjection Unmodified/ 1 * 10⁵ 360 10 — 450 850 36.0 30.3 1500 50% xComparative 1 Unmodified A1 13.30 360 10 — 507 920 41.7 36.1 372 ∘Unmodified A2 0.13 360 10 — 526 963 40.1 36.9 353 ∘ Unmodified A3 13.30360 10 0.2 531 973 41.2 35.7 359 ∘ Unmodified A4 13.30 360 10 5 554 97041.1 34.6 248 ∘ Unmodified A5 0.13 360 10 0.2 547 950 41.8 36.1 349 ∘Unmodified A6 0.13 360 10 5 551 958 41.4 35.9 238 ∘ Modified B1 13.30360 10 — 630 915 45.0 37.2 370 ∘ Modified B2 0.13 360 10 — 641 955 46.938.8 340 ∘ Modified B3 13.30 360 10 0.2 645 954 46.0 38.4 358 ∘ ModifiedB4 13.30 360 10 0.6 649 955 46.0 38.3 235 ∘ Modified B5 13.30 360 10 5652 956 45.9 38.0 237 ∘ Modified C1 0.13 360 10 0.2 619 932 44.8 37.1243 ∘ Modified C2 0.13 360 10 0.6 596 947 43.8 36.7 221 ∘ Modified C30.13 360 10 5 628 954 43.5 36.4 219 ∘ “Unmodified/Comparative 1” is acomparative example of an unmodified PTFE skived film without pressurereduction and pressurization. “Unmodified A1” and “Unmodified A2” areexamples of unmodified PTFE skived films with pressure reduction andwithout pressurization (first method). “Unmodified A3” to “UnmodifiedA6” are examples of unmodified PTFE skived films with pressure reductionand pressurization (second method). “Modified B1” and “Modified B2” areexamples of modified PTFE skived films with pressure reduction andwithout pressurization (first method). “Modified B3” to “Modified B5”and “Modified C1” to “Modified C3” are examples of modified PTFE skivedfilms with pressure reduction and pressurization (second method).“Pressure reduction” represents degree of pressure reduction in thefurnace during thermal fusion. “1 × 10⁵” represents atmosphericpressure. “Pressurization” represents pressure in the furnace duringsecondary thermal fusion in the second method. “Water vapor transmissionamount” represents the amount of water vapor transmission per unit areaafter a lapse of 24 hours from starting of the experiment.

The gasket body subjected to injection has a diameter of 5 mm and alength of 5 mm, and the skived film used in the experiment has athickness of 100 μm. “x” indicates that film tear was observed, and “∘”indicates that film tear was not observed.

According to Table 1, “Unmodified/Comparative 1” in which unmodifiedPTFE was used and thermal fusion was conducted at normal pressure (1×10⁵Pa) exhibits a large water vapor transmission amount and causes filmtear during injection molding.

On the other hand, in “Unmodified A1” and “Unmodified A2” in whichunmodified PTFE was used and thermal fusion was conducted under reducedpressure of 0.013 Pa or 133 Pa according to the first method, the watervapor transmission amount was dramatically reduced by virtue of thethermal fusion treatment under reduced pressure, and film tear was notobserved during injection molding owing to improved elongation. In thesecond method in which pressurization is added, further improvement wasobserved. When modified PTFE is used, these points are further improved.In other words, these seem to be gradually converged and improved as thepressure reduction degree (or pressure reduction degree during primaryfusion) is decreased, and the pressurization degree during the secondaryfusion is increased. FIG. 3 shows data shown in Table 1 selectively.

DESCRIPTION OF THE REFERENCE CHARACTERS

-   -   A pre-filled syringe    -   1 gasket for syringe    -   2 gasket body    -   3 gasket covering film    -   4 syringe barrel    -   5 piston rod    -   6 top cap for syringe    -   7 drug liquid

1. A skived film for covering a surface of a plug for medical purposesobtained by cutting a polytetrafluoroethylene block or a modifiedpolytetrafluoroethylene block subjected to a thermal fusion treatmentunder reduced pressure or subjected to a pressurized thermal fusiontreatment after being subjected to fusion under reduced pressure.
 2. Theskived film for covering a surface of a plug for medical purposesaccording to claim 1, wherein tensile elongation in a machine directionwhich is a longitudinal direction of the film is greater than or equalto 500%.
 3. A plug for medical purposes having a plug body made ofelastomer, wherein the skived film according to claim 1 is overlaid atleast on a sliding part or a liquid contact part of a surface of theplug body.
 4. The plug for medical purposes according to claim 3,wherein the plug is a gasket for syringe, an intermediate gasket forsyringe, a top cap for syringe, or a laminate plug for vial.
 5. Apre-filled syringe produced by hermetically sealing a syringe barrelcharged with a drug liquid with the gasket for syringe or the top capfor syringe according to claim
 4. 6. A method for producing apolytetrafluoroethylene film for covering a surface of a plug formedical purposes, comprising the steps of: pressure-molding powdermaterial of polytetrafluoroethylene or modified polytetrafluoroethylenecharged in a mold to obtain a pressure-molded product havinginterconnected cells inside; subjecting the pressure-molded productobtained by the pressure molding to a thermal fusion treatment underreduced pressure; and cutting the product subjected to the thermalfusion treatment obtained by the thermal fusion treatment to obtain afilm.
 7. A method for producing a polytetrafluoroethylene film forcovering a surface of a plug for medical purposes, comprising the stepsof: pressure-molding powder material of polytetrafluoroethylene ormodified polytetrafluoroethylene charged in a mold to obtain apressure-molded product having interconnected cells inside; subjectingthe pressure-molded product to a primary thermal fusion treatment underreduced pressure to block outlets of communication holes of thepressure-molded product to obtain a product subjected to the primarythermal fusion treatment including only closed cells remaining inside;subjecting the product subjected to the primary thermal fusion treatmentto a secondary thermal fusion treatment under increased pressure toobtain a product subjected to the secondary thermal fusion treatmentfrom which the closed cells have disappeared; and cutting the productsubjected to the secondary thermal fusion treatment to obtain a film. 8.The method for producing a polytetrafluoroethylene film for covering asurface of a plug for medical purposes according to claim 6, wherein thepowder material of polytetrafluoroethylene or modifiedpolytetrafluoroethylene charged in the mold is pressure molded underreduced pressure to obtain a pressure-molded product.
 9. The method forproducing a polytetrafluoroethylene film for covering a surface of aplug for medical purposes according to claim 6, wherein pressurereduction is conducted within a pressure range of 0.013 to 133 Pa. 10.The method for producing a polytetrafluoroethylene film for covering asurface of a plug for medical purposes according to claim 6, wherein athermal fusion treatment temperature is 320 to 400° C.
 11. The methodfor producing a polytetrafluoroethylene film for covering a surface of aplug for medical purposes according to claim 7, wherein a range ofpressurization pressure in the secondary thermal fusion treatment ishigher than or equal to 0.2 Ma.
 12. The method for producing apolytetrafluoroethylene film for covering a surface of a plug formedical purposes according to claim 6, wherein the product subjected tothe thermal fusion treatment has a shape which is a rectangularparallelepiped, a cube, a circular column, or a cylinder.
 13. The methodfor producing a polytetrafluoroethylene film for covering a surface of aplug for medical purposes according to claim 6, wherein the filmproduced by cutting the product subjected to the thermal fusiontreatment has a thickness ranging from 20 to 150 μm.